The candidate, Yutong Liu PhD, is a junior faculty member in the Radiology Department with a strong background in engineering and mathematics, MRI theory, and medical image processing. Dr Liu has had extensive experience in the application of MRI and development of novel image processing methods both during his post-doctoral training and his first years as a junior faculty member. This provides him a solid foundation for biomedical research, but to develop as an independent investigator in neuroscience he requires training in basic neuroscience and practical aspects of performing animal studies. Dr. Liu has assembled a strong mentor and collaborator team with an excellent track record in MRI, neuroscience and image processing research. His primary mentor, Dr. Michael Boska is a leading expert in MRI and MRS. His co-mentor, Dr. Howard Gendelman is an international authority in neurodegenerative diseases. In addition, Dr. Liu will take graduate level courses in neuroscience provided in UNMC. The research project addresses an imperative need in NeuroAIDS research as detailed below. This project will provide training for Dr. Liu in 1) murine brain anatomy and physiology, 2) generation of disease models in mice including irradiation, human cell engraftment, cell acquisition, cultivation, infection and animal surgery, 3) immunohistochemical processing and analysis including, but not limited to slicing, staining and quantification of histopathological staining used for interpretation of results. Dr. Liu will submit a R01 to the NIH by the end of Year 3 of the award focused on the study of neurodegenerative diseases using advanced imaging technologies. His long term career goal is to become an independent investigator in neuroscience. HIV-1 associated neurocognitive disorders (HAND) occurs in the late stage HIV-1 infection and manifests with varying degrees of clinical cognitive, behavioral and motor abnormalities. These range from mild motor/cognitive deficits to overt dementia (HIV-1 associated dementia, HAD). With antiretroviral therapy the cumulative incidence is 25-38% and the prevalence is around 37%. Milder forms affect an additional 30-40% of patients. The chronic and fluctuating forms of HIV dementia are more common. The pathological correlate of HAD is HIV-1 encephalitis (HIVE). The presence of activated microglia and brain macrophages with lower levels of virus is a central pathological feature of disease. Tests that can clearly distinguish HAND from other diseases of the nervous system that occur during progressive HIV-1 infection are needed for definitive diagnosis, disease progression tracking and therapeutic monitoring. Murine models of HIVE and HAND have been developed at the University of Nebraska Medical Center. The objective of this proposal is to develop in-vivo manganese enhanced 3D multispectral magnetic resonance microscopy (MRM) that will serve as a biomarker for HAND. In vivo manganese enhanced multispectral MRM (MEmMRM) and MRM data analysis techniques will be developed to determine the time course of neuronal loss, macrophage/microglial activation and astrocytosis in the murine HIVE and HAND models. MEmMRM results in diseased mice will be confirmed with controls and histopathological analysis.

Public Health Relevance

The cumulative incidence of HIV-1 associated dementia in the Western world is 25-38% with highly active antiretroviral therapy (HAART) and the prevalence is around 37%. Milder forms affect an additional 30-40% of patients. Although a number of clinical, laboratory and radiological tests are available to aid in diagnosis, none are conclusive. This project will provide a biomarker of HIV-1 associated neurocognitive disorders for definitive diagnosis, disease progression tracking and therapeutic monitoring using MRI on murine models.